科普性文章---三光气是不是光气的安全替代品

A Safer Alternative to Phosgene?Livius Cotarca,?,* Thomas Geller,? and Jo?zsef Re?pa?si§?LC Consulting, 33052 Cervignano del Friuli (UD), Italy?Product Supply, Crop Science Division, Bayer AG, 41539 Dormagen, Germany§SONEAS Hungary, Illatos u?t 33, Budapest, H-1097, HungaryABSTRACT:?Bis(trichloromethyl)carbonate (BTC, triphosgene) is a versatile compound that enables highly efficient syntheses. In addition, because of its solid state, it is a very convenient compound for all-scale phosgenations. Consequently, this compound is favored as a phosgene substitute in research and development and in all-scale production. Although BTC is highly toxic, safe handling is possible as long as the properties and chemical reactivity of this compound are understood and considered. However, branding as “safe phosgene” or “safer phosgene” is misleading. The solid state of BTC leads to the misconception that there is no significant exposure. However, the vapor pressure is sufficiently high to easily result in toxic concentrations. In addition, proper monitoring is not yet possible. Proper use of BTC could be more complex than the handling of phosgene itself. However, handling of BTC is normally always associated with phosgene and has its own toxicity. Therefore, the use of BTC will become more regulated in the future, which will directly increase responsibility in route selection during process development. A stringent safety concept for phosgenations using BTC is necessary. Because of the interconnection with phosgene, the safety concept forBTC will likely be an extended version of the safety concept for phosgene.The popularity of BTC is directly related to its physical properties, that is, its solid form, its low tendency to evaporate (vapor pressure at ambient temperature appr. 0.4 mbar), and commercial availability. In addition, BTC is currently not as tightly regulated as phosgene, and its reputation is, without wellfounded reasons, much better than that of phosgene. Because of the stability of BTC at ambient temperature and its solid-state handling, the transportation, storage, handling, and processing of BTC appear to be more convenient than for phosgene. On all and medium scales (laboratories and pilot plants), BTC provides substantial operational convenience because exact amounts can be weighed easily. Furthermore, no facilities for carbon monoxide or chlorine (or phosgene cylinder) handling are necessary. This ease of handling helps pharmaceutical and fine chemicals producers perform “phosgenations” in pilot plants and kilo laboratories, which are normally not adequately equipped to use phosgene directly.For various reasons, including commercial aspects, suppliers and most published literature brand BTC as “safe phosgene”, or “safer phosgene,” or “green phosgene.” The branding as “safe phosgene” is particularly misleading. New research results clearly show that BTC is at least as dangerous as phosgene.?Its toxicity is only partly related to phosgene, which is released as a byproduct in the off-gas phases during reactions; BTC has a distinctive toxicity profile that differs substantially from that of phosgene.??The misconception of a “safer phosgene” is dramatically underscored by the fact that, within the last 10 years, several significant incidents with phosgene were de facto incidents with BTC。A particularly important but widely unknown behavior of BTC is that it sublimes even at room temperature. This fact is of utmost importance for the handling of BTC including safety procedures.Although BTC is a solid, it has a low but significant vapor pressure and sublimes. At room temperature, the BTC concentration of a saturated atmosphere is 4.2 g/m3, approximately 100 times higher than the LC50 value for rats (41.5 mg/m3), (see Toxicology section, infra). Ubichem reports an even higher value (11.6 g/m3) for the calculated BTC concentration in a saturated atmosphere.? Because of the high lipophilicity of BTC, it does not react directly with water. Under certain conditions, BTC vapor can even pass a sodium hydroxide scrubber unchanged and may be found as a deposit behind the scrubber. This problem must be solved individually for each process. In industrial environments, handling is critical because no detector calibrated for BTC is commercially available; thus, discrimination between phosgene and BTC is not yet possible, meaning that relevant concentrations of BTC may remain undetected.In summary, three decomposition pathways are identified in the literature:(i) BTC decomposes into three molecules of phosgene below the boiling point (206 °C) in the presence of initiators;(ii) At lower temperatures (e.g., during distillation), BTC decomposes into phosgene and diphosgene. Upon heating, rapid decomposition to phosgene occurs when BTC is mixed with powdered activated carbon or Lewis acids;(iii) Decomposition to carbon dioxide, carbon tetrachloride and phosgene can occur; the off-gases were yzed through thermogravimetric ysis?Fourier transform infrared (TGAFTIR) ysis.The odor of BTC or phosgene is definitely inappropriate as a?warning signal; toxicologically relevant amounts of these?compounds remain undetected and can accumulate over time?(e.g., phosgene: >0.13 ppm odor perception, >1.5 ppm?recognition of odor, >3 ppm irritations; 50?150 ppm·min?subclinical effects; >150 ppm·min pulmonary edema likely;?example: 1 ppm phosgene in air results after >2.5 h in a lung?edema).BTC is a versatile compound that enables highly efficient syntheses. In addition, because of its solid state, it is a very convenient compound for all-scale phosgenations. Consequently, this compound is favored as a phosgene substitute in research and development and in all-scale production. Although BTC is highly toxic, safe handling is possible as long as the properties and chemical reactivity of this compound are understood and considered. However, branding as “safer phosgene” or “safe phosgene” is misleading. The solid state ofBTC leads to the misconception that there is no significant exposure. However, the vapor pressure is sufficiently high to easily result in toxic concentrations. In addition, proper monitoring is not yet possible. Proper use of BTC could be more complex than the handling of phosgene itself. Currently, handling of BTC is not as tightly regulated as phosgene. However, handling of BTC is normally always associated with phosgene and has its own toxicity. Therefore, the use of BTC may become more regulated in the future, which ?will directly increase responsibility in future route selection during process development.The information and thoughts in this publication should only be seen as an impulse for the establishment of an own safety concept. An individual safety ysis is necessary since processes and circumstances can vary in a wide range. However, a stringent safety concept for phosgenations using BTC is a must and will be most likely become a subject of regulations and inspections in the future. Due to the interconnection with phosgene, it can be expected that the safety concept for BTC will have to be an extended version of safety concept for phosgene.